The mechanisms of resistance to sorafenib and lenvatinib have been attributed to overexpression of EGFR, abnormal changes in the JAK/STAT pathway, activation of autophagy allowing HCC cells to survive nutrient deprivation, hypoxia within the tumor mass inducing VEGF through HIF-1α, dysregulated epigenetic regulation and EMT. The gene discussed is EGFR; the disease is hepatocellular carcinoma.